Real-World Resmetirom Data Show Liver Stiffness Gains in MASH

Real-world data presented at The Liver Meeting 2026 showed resmetirom (Rezdiffra) improved or stabilized liver stiffness in most patients with metabolic dysfunction-associated steatohepatitis (MASH) treated in routine practice, according to Madrigal Pharmaceuticals.¹ Across several retrospective analyses, 37% to 55% of patients with paired liver stiffness measurements (LSM) achieved an improvement of at least 25% at approximately 1 year.¹

Madrigal announced the findings, drawn from electronic health record, claims, and pharmacy databases, on November 5, 2026, alongside poster presentations at the American Association for the Study of Liver Diseases (AASLD) meeting in Denver, Colorado.¹

“Not every medicine delivers the same results in real-world clinical practice that we see in carefully controlled clinical trials, particularly when treating a complex, chronic disease like MASH,” Parvez Mantry, MD, at The Liver Institute at Methodist Dallas Medical Center, said in a statement. “What makes these findings so encouraging is the remarkable consistency of improvement we're seeing across multiple real-world studies of Rezdiffra, involving different patient populations and clinical settings. For physicians treating MASH, this growing body of evidence provides important reassurance that the benefits observed in these trials are translating into everyday patient care.”

The oral thyroid hormone receptor-beta (THR-β) agonist received US Food and Drug Administration (FDA) accelerated approval in March 2024 for adults with noncirrhotic MASH and moderate to advanced fibrosis (F2–F3), based on results from the phase 3 MAESTRO-NASH trial.1,2 In the new real-world analyses, up to 53% of patients were receiving glucagon-like peptide-1 (GLP-1)–based therapy alongside resmetirom.¹

How Did Resmetirom Affect Liver Stiffness in Real-World Practice?

In a retrospective Truveta cohort of 150 patients with paired LSM, 55% achieved an improvement of at least 25% at 12 months, and 48.0% achieved an improvement of at least 30%. Overall, 93% of patients improved or remained stable, and 67% moved to a lower predefined LSM range. Across the broader Truveta analysis, mean LSM decreased by 2.5 kPa from baseline at 12 months.¹

A subgroup analysis of 2,488 Truveta patients stratified by diabetes, obesity, GLP-1 receptor agonist use, and statin use showed statistically significant improvements in mean LSM and liver fat across subgroups.¹ Between 89% and 98% of patients in each subgroup improved or remained stable.

Results were directionally consistent in other datasets. In Trio Health data, 45% of 195 patients achieved an LSM improvement of at least 25% at 12 months, and 44% of a separate group of 347 patients with documented fibrosis stages improved by at least one stage.¹ In a Gastro Health/Latica cohort, 32 of 46 patients with baseline LSM between 10 and less than 20 kPa moved below 10 kPa at follow-up, while 37% of 35 patients at Methodist Dallas Medical Center achieved an improvement of at least 25% .¹

What Cardiometabolic and Safety Findings Were Reported with Resmetirom?

In the Truveta analysis, mean alanine aminotransferase (ALT) decreased by 16.2 U/L, LDL cholesterol by 15.5 mg/dL, and triglycerides by 41.0 mg/dL from baseline at 12 months; Madrigal described all of these changes as statistically significant.¹ In Trio Health data, 48% of patients had an ALT reduction of at least 20%, and 54% had a clinically meaningful reduction in controlled attenuation parameter (CAP) of more than 40 dB/m.¹ Claims-based Optum Market Clarity data also showed statistically significant reductions in liver enzymes and select cardiometabolic measures at 12 months.¹

In the Gastro Health/Latica cohort, 11% of patients experienced at least one adverse event. The most frequent were diarrhea (7%), nausea (4%), pruritus (2%), and vomiting (2%).¹ Resmetirom carries warnings for hepatotoxicity and gallbladder-related events and is not recommended with gemfibrozil.¹

Persistence analyses included a retrospective CVS Healthspire pharmacy cohort of 11,469 patients, along with claims-based data.¹ Up to 89% of patients remained on therapy at 6 months and up to 72% at 12 months, using a 60-day treatment-gap definition.¹

"These new data represent an important expansion of the real-world evidence supporting [resmetirom] as a foundational therapy for patients with MASH," said David Soergel, MD, Chief Medical Officer of Madrigal. "Across multiple studies and diverse patient populations, we are seeing robust improvements in noninvasive measures of liver health consistent with the positive results observed in the pivotal Phase 3 trial of [resmetirom]. The findings also provide encouraging evidence that most patients are staying on therapy over time. Together, these results reinforce the strong real-world effectiveness, safety and tolerability profile of [resmetirom], and provide valuable insight into how the medication is being used in everyday clinical practice.”

References

1. Madrigal Pharmaceuticals. Madrigal announces new real-world data at AASLD 2026 demonstrating improvements in liver stiffness and cardiometabolic health markers with Rezdiffra. GlobeNewswire. Published November 5, 2026. Accessed November 5, 2026. https://www.globenewswire.com/news-release/2026/11/05/3396655/0/en/madrigal-announces-new-real-world-data-at-aasld-2026-demonstrating-improvements-in-liver-stiffness-and-cardiometabolic-health-markers-with-rezdiffra.html

2. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000